The invention relates in general to the field of microfluidics, and in particular to vertical microfluidic probe heads.
Microfluidics deals with the behavior, precise control and manipulation of small volumes of fluids that are typically constrained to micrometer-length scale channels and to volumes typically in the sub-milliliter range. Prominent features of microfluidics originate from the peculiar behavior that liquids exhibit at the micrometer length scale. Volumes well below one nanoliter can be handled and analyzed by fabricating structures with lateral dimensions in the micrometer range. Reactions that are limited at large scales (by diffusion of reactants) can be accelerated. Finally, parallel streams of liquids can possibly be accurately and reproducibility controlled, allowing for chemical reactions and gradients to be made at liquid/liquid and liquid/solid interfaces.
More specifically, typical volumes of fluids in microfluidics range from 10−15 L to 10−5 L and are transported, circulated or more generally moved via microchannels with a typical diameter of 10−7 m to 10−4 m. At the microscale, the behavior of fluids can differ from that at a larger, e.g., macroscopic, scale, such that surface tension, viscous energy dissipation and fluidic resistance may become dominant characteristics of the fluid flow. The Reynolds number, which compares the effects of fluid momentum and viscosity, may decrease to such an extent that liquid flows become laminar rather than turbulent.
In addition, at the microscale, fluids do not necessarily chaotically mix, due to absence of turbulence, and transport of molecules or small particles between adjacent fluids often takes place through diffusion. As a consequence, certain chemical and physical fluid properties (such as concentration, pH, temperature and shear force) may become deterministic. This makes it possible to obtain more uniform chemical reaction conditions and higher grade products in single and multi-step reactions.
Microfluidic devices generally refer to microfabricated devices, which are used for pumping, sampling, mixing, analyzing and dosing liquids. A microfluidic probe is a device for depositing, retrieving, transporting, delivering, and/or removing liquids, in particular liquids containing chemical and/or biochemical substances. For example, microfluidic probes can be used in the fields of diagnostic medicine, pathology, pharmacology and various branches of analytical chemistry. Microfluidic probes can also be used for performing molecular biology procedures for enzymatic analysis, deoxyribonucleic acid (DNA) analysis and proteomics.
In particular, a concept of microfluidic devices is known, which is referred to as “vertical microfluidic probe head” in the literature, see e.g., “A Vertical Microfluidic Probe”, by G. V. Kaigala, R. D. Lovchik, U. Drechsler, and E. Delamarche, Langmuir, 2011, 27 (9), pp 5686-5693. The microfluidic probe head comprises a body, e.g., a silicon substrate, which has an edge surface forming part of the processing surface of the device. Liquid channels or microchannels are formed at an interface between two layers, by grooving the body up to the edge surface and closing it with a lid, which simplifies the fabrication of the head. In particular, such devices may comprise a liquid dispenser(s), designed to dispense liquid via an orifice terminating a first one of the channels, and a liquid aspirator(s) aspirates liquid via another orifice and a second one of the channels.
Such devices allow a hydrodynamic flow confinement (HFC) of the processing liquid to be obtained. In other words, a laminar flow of processing liquid is dispensed from an aperture, which liquid is spatially confined within an environmental liquid (or immersion liquid).
Microfluidic probes (MFPs) are known, which may create and sustain a hydrodynamic flow confinement (HFC) with footprints on the order of 100 μm2. To process a large area with a HFC, the current approach is to scan over the entire area sequentially. Such a sequential processing is time consuming.
There are several scenarios where large areas need be processed while retaining important aspects of the HFC. For example, processing tissue sections for immunohistological analysis (detection protein expression levels) requires processing at the cm-scale. Detecting (“sensing”) protein expression profiles, for example, is important for some medical decisions and associated analytics.
Current vertical MFPs cannot sustain a HFC at cm-length scale. More generally, current vertical MFPs are not suited for processing large areas.